Francisco José Suárez Domínguez

Expression of E-cadherin in squamous cell carcinomas of the supraglottic larynx with correlations to clinicopathological features

The aim of this study was to investigate the prognostic significance of E-cadherin expression in squamous cell carcinomas of the supraglottic larynx. 101 primary carcinomas were retrospectively studied. The level of E-cadherin expression was determined by immunohistochemistry. There was a significant correlation between decreased E-cadherin expression and the presence of nodal metastases (P=0.007). T-stage (P=0.025) and histological grade (P=0.043) were also associated with nodal metastases. Multivariate analysis confirmed that these three parameters were independent predictors of nodal metastases. Decreased E-cadherin expression also correlated with an increase in recurrence rates (P=0.019). However, in multivariate analysis only pathological N-stage was significantly associated with disease-specific survival. We conclude that E-cadherin is an independent predictor of nodal metastases in supraglottic squamous cell carcinomas. Determination of E-cadherin expression levels might be useful in identifying patients with clinically negative lymph nodes who are at risk of occult metastases, allowing more effective treatment strategies to be implemented.

P53 expression in squamous cell carcinomas of the supraglottic larynx and its lymph node metastases : New results for an old question

Although p53 overexpression is frequent in head and neck squamous cell carcinomas (HNSCCs), controversy remains regarding the prognostic significance of that overexpression. The objective of this study was to investigate the expression pattern and prognostic significance of p53 expression in HNSCC of the same location, treated in the same way, and with long‐term follow‐up.

Fine Needle Aspiration of Breast Masses

OBJECTIVE: To determine the diagnostic efficacy of breast fine needle aspiration (FNA) in the routine practice of a community hospital. STUDY DESIGN: The study group consisted of 1,398 consecutive FNA biopsies of the female breast performed at our institution during a five-year period; 450 (32%) had histologic follow-up. Both FNA and the histologic diagnosis were compared in order to establish the accuracy, efficiency and safety of the FNA breast technique. RESULTS: The sensitivity of the FNA procedure was 93.49% and specificity 95.73%, with a predictive value for a positive diagnosis of 93.49% and for a negative diagnosis, 95.73%. The overall diagnostic accuracy was 94.84%, and the sensitivity of cytologic diagnosis was 98.75%. The false negative and false positive rates were 2.5%, including 10 cases with suspicious diagnoses and only 1 false positive diagnosis (0.23%). The false positive and false negative cases were recorded as having no effect or a minimal effect on patient management, and no mastectomy was performed because of this FNA diagnosis. CONCLUSION: FNA breast biopsy is an efficient tool for diagnosis when performed by surgical pathologists with cytologic training but not exclusively dedicated to cytopathology.

Clinicopathologic Significance of Expression of CD44s and CD44v6 Isoforms in Squamous Cell Carcinoma of the Supraglottic Larynx

CD44 splice variants are assumed to have a critical role in the malignant progression of many human tumors. However, the clinical significance of CD44 expression is not yet understood. The aim of this study was to investigate the prognostic significance of expression of CD44s and CD44v6 isoforms in squamous cell carcinomas of the supraglottic larynx. CD44s and CD44v6 expression was determined by immunohistochemical analysis of paraffin-embedded tissue specimens from 101 patients. There was a significant correlation between decreased CD44s or CD44v6 expression and a poorer histologic differentiation. No relationship was observed with T stage or nodal metastasis. Decreased CD44s expression, but not CD44v6 expression, correlated with increased recurrence rates. There was no correlation between the decreased expression of any isoform tested and survival. These data confirm a reduction of CD44s and CD44v6 expression in poorly differentiated tumors. However, these changes do not offer a useful adjunct to current prognostic indicators.

Expression of E-cadherin, CD44s, and CD44v6 in laryngeal and pharyngeal carcinomas.

OBJECTIVE Tumors arising from different sites of the head and neck area have very different clinical behavior. Loss or reduction of expression of adhesion molecules has been assumed to play a critical role in the development of head and neck carcinomas. The aim of this study is to determine if there are differences in the expression of adhesion molecules E-cadherin, CD44s, and CD44v6 in pharyngeal and laryngeal squamous-cell carcinomas. MATERIALS AND METHODS E-cadherin, CD44s, and CD44v6 expression was determined by immunohistochemistry in paraffin-embedded tissue specimens from 72 patients with squamous-cell carcinoma, 37 of the pharynx and 35 of the larynx. RESULTS Expression of CD44s was significantly lower in pharyngeal than in laryngeal tumors (P =.01). No differences in the expression of E-cadherin and CD44v6 were observed between these sites. CONCLUSIONS These data suggest that there are some differences at molecular level between the different subsites of head and neck cancer.

Utility of MS-MLPA in DNA methylation profiling in primary laryngeal squamous cell carcinoma

OBJECTIVES Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay is a method that has rarely been exploited in DNA methylation profiling of laryngeal squamous cell carcinoma (LSCC). MATERIAL AND METHODS Methylation of the gene was investigated by MS-MLPA in a well-characterized series of 53 LSCC and 30 samples of healthy mucosa. Aberrant promoter hypermethylation was confirmed using bisulfite pyrosequencing, and methylation-specific. RESULTS Promoter hypermethylation was observed in 36 of the 53 patients (68%). CDKN2B (28%), APC (17%), RARβ (15%), DAPK1 (11%) and CHFR (11%) were most frequently hypermethylated. Aberrant methylation of CHFR was mainly a late-stage event. Methylation-specific polymerase chain reaction and bisulfite pyrosequencing confirmed aberrant methylation for CDKN2B, APC and DAPK1. CONCLUSION Promoter methylation profiling of LSCC using MS-MLPA identified CDKN2B, DAPK1, RARβ, APC, and CHFR as frequent epigenetic events. The clinical implications of these genes as biomarkers are highly relevant as attractive targets for cancer therapy, given the reversible nature of epigenetic gene silencing.

From laryngeal epithelial precursor lesions to squamous carcinoma of the larynx: the role of cell cycle proteins and β-catenin

Novel markers to accurately predict the risk of malignant transformation in laryngeal epithelial precursor lesions (EPL) are needed. We tried to identify some molecular alterations occurring in laryngeal tumorigenesis. In this study, 60 paraffin-embedded EPL and 17 metachronous invasive carcinomas were immunostained for markers associated with proliferation (Ki67), cell cycle control (p53, p21, p16, p27, cyclin D1), and cell adhesion and invasion (laminin and β-catenin). Aberrant expression of p16 and p53 and positivity at cytoplasm for β-catenin and cyclin D1 were detected significantly in EPL with progression to invasive laryngeal carcinoma. All cases with basal and suprabasal reactivity of p53 showed β-catenin overexpression. We found that β-catenin protein expression increased significantly with the grade of dysplasia. This is one of the studies with the largest number of laryngeal EPL and invasive carcinoma studied sequentially. Our data confirm the role of some cell cycle regulatory proteins in the development of laryngeal carcinoma. Cytoplasmic retention of β-catenin in EPL seems to be related with more aggressive biological behavior. Combined increased p53 and cytoplasmic β-catenin protein expression could be biologically important in laryngeal tumorigenesis. Further research is required to clarify the involvement of β-catenin in the mechanism associated with malignant transformation in laryngeal tissues.

Genetic and protein markers related to laryngeal epithelial precursor lesions and their neoplastic progression

Abstract Conclusion: Various biomarkers might ultimately prove to have prognostic value and could be clinically relevant. It is mandatory confirm the prognostic power of these markers in large, well-designed, and prospective studies. Objective: The aim of this study was to investigate the possible role of specific genes and proteins in laryngeal tumorigenesis. Methods: Genetic analysis by multiple ligation-dependent probe amplification and analysis of protein expression by immunohistochemistry were carried out in a series of 50 tissue samples. Results: In the smoker normal mucosa group TP53 loss was predominant, whereas in the epithelial precursor lesions (EPLs) CDKN2A loss and BCL2L1 gain were most frequent. EPL with progression presented CTNNB1 loss. Positivity at cytoplasm for β-catenin, cyclin D1 and p53 was detected in all EPL cases with progression to invasive carcinoma. Multivariate analysis showed that expression of β-catenin and loss of CTTNB1 were associated with laryngeal cancer risk.

Numerical Analysis of the Behaviour of Tooth Intrarradial Posts by the Finite Element Method

The aim of this work is to study the behaviour of a carbon/epoxi post housed in a canine tooth after endodontic treatment in order to support the typical loads present during mastication. The three-D basic design of the dental piece consisting of tooth + post was carried out with a three-dimensional parametric design program. We study the stresses and displacements of the different elements of the dental piece under normal load conditions, and present the results and conclusions.The aim of this work is to study the behaviour of a carbon/epoxi post housed in a canine tooth after endodontic treatment in order to support the typical loads present during mastication. The three-D basic design of the dental piece consisting of tooth + post was carried out with a three-dimensional parametric design program. We study the stresses and displacements of the different elements of the dental piece under normal load conditions, and present the results and conclusions.

Risk factors for loco-regional recurrence in breast cancer patients: a retrospective study

Background Although fairly uncommon, loco-regional recurrence in breast cancer (BC) has major consequences for the patient. Several predictors for locoregional have been previously reported from large randomized clinical trials mainly from Europe & North America; data from other geographical areas are somewhat scarce. Here we performed a retrospective review of medical records in a single academic center in Chile, searching for predictors of breast tumor recurrence. Results Median patient follow up was 61 months, 5 year overall survival (OS) rate was 94.2% (95% CI 93–95.3). We found that 108 out of 2,754 (5.3%) patients had loco-regional recurrence. The 2-year loco-regional control was 98% (95% CI 97.3–98.7) and 5-year was 94% (95% CI 92.6–95.4). Univariate analysis showed a correlation between recurrence and being <50 year-old, positive surgical margins, advanced stage, subtype, and presence of LVI and omission of adjuvant radiotherapy. Only the absence of adjuvant RT was predictor of locoregional recurrence in multivariable (p < 0.001). Conclusions Our study population presents high local control of BC. Age, surgical margins, stage, molecular subtype and absence of adjuvant radiotherapy were associated with loco-regional recurrence. Prospective trials and long-term follow up are required in order to confirm these results. Materials and Methods We analyzed medical records from 2,201 BC patients at the Pontificia Universidad Católica de Chile from 1997 to 2016. Collected data included: age at diagnosis, tumor size, axillary involvement, molecular subtype, margin status, histological grade, lympho-vascular invasion (LVI) and ipsilateral recurrence.